Therapy optimization in heart failure patients based on minute ventilation patterns

ABSTRACT

A method and system for operating a rate-adaptive pacemaker utilizing minute ventilation to measure exertion level. The method is applicable to heart failure patients who exhibit an oscillatory minute ventilation pattern.

CROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] This application claims the benefit of U.S. ProvisionalApplication Serial No. 60/273,778, filed Mar. 2, 2001, under 35 U.S.C.119(e).

FIELD OF THE INVENTION

[0002] This invention pertains to apparatus and methods for cardiacrhythm management. In particular, the invention relates to improvementsin providing rate-adaptive and/or resynchronization pacing therapy toheart failure patients.

BACKGROUND

[0003] Cardiac pacemakers are cardiac rhythm management devices thatattempt to compensate for the heart's inability to pace itselfadequately in order to meet metabolic demand, termed bradycardia pacing.A pacemaker is an implantable battery-powered electronic device thatresponds to sensed cardiac events and elapsed time intervals by changingits functional states so as to properly interpret sensed data anddeliver pacing pulses to the heart at appropriate times. Additionalsensing of physiological data allows some pacemakers to change the rateat which they pace the heart in accordance with some parametercorrelated to metabolic demand. Such pacemakers are called rate-adaptivepacemakers.

[0004] Heart failure is a clinical syndrome in which an abnormality ofcardiac function causes cardiac output to fall below a level adequate tomeet the metabolic demand of peripheral tissues and is usually referredto as congestive heart failure (CHF) due to the accompanying venous andpulmonary congestion. CHF can be due to a variety of etiologies withischemic heart disease being the most common. Some CHF patients sufferfrom some degree of AV block or are chronotropically deficient such thattheir cardiac output can be improved with conventional bradycardiapacing. Such pacing, however, may result in some degree ofuncoordination in atrial and/or ventricular contractions due to the wayin which pacing excitation is spread throughout the myocardium withoutuse of the normal specialized conduction pathways. The resultingdiminishment in cardiac output may be significant in a CHF patient whosecardiac output is already compromised. Intraventricular and/orinterventricular conduction defects are also commonly found in CHFpatients. In order to treat these problems, cardiac rhythm managementdevices have been developed which provide electrical pacing stimulationto one or more heart chambers in an attempt to improve the coordinationof atrial and/or ventricular contractions, termed cardiacresynchronization therapy.

[0005] Heart failure patients may be treated with pacemakers thatprovide rate-adaptive pacing and/or resynchronization therapy. Thepresent invention is concerned with improving the way in which suchtherapies are delivered to these patients.

SUMMARY OF THE INVENTION

[0006] The present invention relates to a cardiac pacemaker in which thepresence or absence of oscillatory minute ventilation patterns aredetected and used to optimize pacing therapy in heart failure patients.It has been found that patients who are suffering from some degree ofheart failure commonly exhibit an oscillatory minute ventilation patternduring rest and at exertion levels up to the anaerobic threshold.Accordingly, in one embodiment, minute ventilation values are measuredas a patient's exertion level increases, with the resulting minuteventilation signal filtered to extract the oscillatory component. Theoscillatory component is determined to be present if its amplitude isabove a specified threshold value. If the oscillatory component fallsbelow the specified threshold value as the patient's exertion levelincreases, the anaerobic threshold can be assumed to have been reachedat that particular exertion level. In order to optimize the operation ofa rate-adaptive pacemaker using a dual-slope rate response curve, thebreakpoint of the curve is then set to the minute ventilation value atwhich the oscillatory minute ventilation pattern ceased.

[0007] In a rate-adaptive pacemaker using minute ventilation as ameasure of exertion level, an oscillatory minute ventilation pattern maycause inappropriate adjustments to be made to the pacing rate. Inanother embodiment, therefore, a rate-adaptive pacemaker operating in aheart failure patient known to exhibit an oscillatory minute ventilationpattern is programmed to utilize another exertion level sensor tocross-check minute ventilation values before adjusting the pacing rate.For example, an activity level sensor such as an accelerometer can beused to provide a measure of the patient's activity level which is thencompared with a minute ventilation reading. Only if the minuteventilation reading and the corresponding activity level measurementmatch within a specified range is the pacing rate adjusted. In this way,changes in minute ventilation due solely to the oscillatory componentare ignored and not allowed to cause inappropriate adjustments to thepacing rate.

[0008] It has also been found that the degree to which heart failurepatients exhibit an oscillatory minute ventilation pattern correlateswith the degree to which their cardiac output is compromised.Measurement of oscillatory minute ventilation patterns can thus be usedto monitor the effectiveness of a pacemaker configured to delivercardiac resynchronization therapy, which therapy has been shown to bebeneficial in raising the cardiac output of heart failure patients. Inparticular embodiments, measurement of the oscillatory component ofminute ventilation can either be used to automatically adjustresynchronization pacing parameters or be reported to a clinician via anexternal programmer so that appropriate therapy modifications can bemade.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009]FIG. 1 illustrates an oscillatory minute ventilation pattern.

[0010]FIGS. 2A and 2B depicts rate-response curves.

[0011]FIG. 3 is a diagram of a rate-adaptive pacemaker.

[0012]FIG. 4 is a flow diagram illustrating a particular implementationof the present method for adjusting the breakpoint of a dual-slope rateresponse curve.

DETAILED DESCRIPTION

[0013] Based upon cardiopulmonary exercise tests, it has been found thatheart failure patients consistently exhibit an oscillatory minuteventilation pattern, with the period of the oscillations typicallygreater than one minute. It has also been found that the oscillatorypattern occurs at the onset of exercise but disappears once the patientreaches the anaerobic threshold. FIG. 1 illustrates an example of anoscillatory minute ventilation pattern in which minute ventilation MV isplotted against time T as a patient exercises with increasing intensity.As shown in the figure, the oscillations cease when the patient reachesan exertion level corresponding to the anaerobic threshold AT.Additionally, the magnitude of the oscillations decreases when effectivetherapy is instituted that increases cardiac output, such as ventricularresynchronization therapy. Although the cause of the oscillatorybehavior is not known with certainty, it is supposed that neuro-hormonalmechanisms are involved. The present invention relates to a method andapparatus for utilizing detection of an oscillatory minute ventilationpattern in order to optimize rate-adaptive and/or resynchronizationpacing in heart failure patients.

[0014] 1. Bradycardia Pacing

[0015] The most common condition for which pacemakers are used is thetreatment of bradycardia. Permanent pacing for bradycardia is indicatedin patients with symptomatic bradycardia of any type as long as it islikely to be permanent or recurrent and is not associated with atransient condition from which the patient may recover.Atrio-ventricular conduction defects (i.e., AV block) that are fixed orintermittent and sick sinus syndrome represent the most commonindications for permanent pacing. Modern pacemakers are typicallyprogrammable so that they can operate in any mode which the physicalconfiguration of the device will allow. Such modes define which heartchambers are paced, which chambers are sensed, and the response of thepacemaker to a sensed P wave or R wave (i.e., an atrial or ventricularsense, respectively). A three-letter code is used to designate a pacingmode where the first letter refers to the paced chamber(s), the secondletter refers to the sensed chamber(s), and the third letter refers tothe response.

[0016] Pacemakers can enforce a minimum heart rate either asynchronouslyor synchronously. In asynchronous pacing, the heart is paced at a fixedrate irrespective of intrinsic cardiac activity. There is thus a riskwith asynchronous pacing that a pacing pulse will be deliveredcoincident with an intrinsic beat and during the heart's vulnerableperiod which may cause fibrillation. Most pacemakers for treatingbradycardia today are therefore programmed to operate synchronously in aso-called demand mode where sensed cardiac events occurring within adefined interval either trigger or inhibit a pacing pulse. Inhibiteddemand pacing modes utilize escape intervals to control pacing inaccordance with sensed intrinsic activity. In an inhibited demand mode,a pacing pulse is delivered to a heart chamber during a cardiac cycleonly after expiration of a defined escape interval during which nointrinsic beat by the chamber is detected. If an intrinsic beat occursduring this interval, the heart is thus allowed to “escape” from pacingby the pacemaker. Such an escape interval can be defined for each pacedchamber. For example, a ventricular escape interval can be definedbetween ventricular events so as to be restarted with each ventricularsense or pace. The inverse of this escape interval is the minimum rateat which the pacemaker will allow the ventricles to beat, sometimesreferred to as the lower rate limit (LRL).

[0017] In atrial tracking pacemakers (i.e., VDD or DDD mode), anotherventricular escape interval is defined between atrial and ventricularevents, referred to as the atrio-ventricular interval (AVI). Theatrio-ventricular interval is triggered by an atrial sense or pace andstopped by a ventricular sense or pace. A ventricular pace is deliveredupon expiration of the atrio-ventricular interval if no ventricularsense occurs before. Atrial-tracking ventricular pacing attempts tomaintain the atrio-ventricular synchrony occurring with physiologicalbeats whereby atrial contractions augment diastolic filling of theventricles. If a patient has a physiologically normal atrial rhythm,atrial-tracking pacing also allows the ventricular pacing rate to beresponsive to the metabolic needs of the body.

[0018] A pacemaker can also be configured to pace the atria on aninhibited demand basis. An atrial escape interval is then defined as themaximum time interval in which an atrial sense must be detected after aventricular sense or pace before an atrial pace will be delivered. Whenatrial inhibited demand pacing is combined with atrial-triggeredventricular demand pacing (i.e., DDD mode), the lower rate limitinterval is then the sum of the atrial escape interval and theatrio-ventricular interval.

[0019] 2. Rate-adaptive Pacing

[0020] In chronotropically competent patients in need of ventricularpacing, atrial tracking modes such as DDD or VDD are desirable becausethey allow the pacing to track the physiologically normal atrial rhythm,which causes cardiac output to be responsive to the metabolic needs ofthe body. Atrial tracking modes are contraindicated, however, inpatients prone to atrial fibrillation or flutter or in whom a reliableatrial sense cannot be obtained. In the former case, the ventricles willbe paced at too high a rate. Failing to sense an atrial P wave, on theother hand, results in a loss of atrial tracking which can lead tonegative hemodynamic effects because the pacemaker then reverts to itsminimum ventricular pacing rate. In pacemaker patients who arechronotropically incompetent (e.g., sinus node dysfunction) or in whomatrial-triggered modes such as DDD and VDD are contraindicated, theheart rate is determined solely by the pacemaker in the absence ofintrinsic cardiac activity. That heart rate is the lower rate limit orLRL.

[0021] Pacing the heart at a fixed rate as determined by the LRL settingof the pacemaker, however, does not allow the heart rate to increasewith increased metabolic demand. Cardiac output is determined by twofactors, the stroke volume and heart rate, with the latter being theprimary determinant. Although stroke volume can be increased duringexercise, the resulting increase in cardiac output is usually notsufficient to meet the body's metabolic needs unless the heart rate isalso increased. If the heart is paced at a constant rate, as for exampleby a VVI pacemaker, severe limitations are imposed upon the patient withrespect to lifestyle and activities. It is to overcome these limitationsand improve the quality of life of such patients that rate-adaptivepacemakers have been developed. Rate-adaptive pacemakers operate so asto vary the lowest rate at which the heart is allowed to beat inaccordance with one or more physiological parameters related tometabolic demand.

[0022] The body's normal regulatory mechanisms act so as to increasecardiac output when the metabolic rate is increased due to an increasedexertion level in order to transport more oxygen and remove more wasteproducts. One way to control the rate of a pacemaker, therefore, is tomeasure the metabolic rate of the body and vary the pacing rate inaccordance with the measurement. Metabolic rate can effectively bedirectly measured by, for example, sensing blood pH or blood oxygensaturation. Practical problems with implementing pacemakers controlledby such direct measurements, however, have led to the development ofpacemakers that are rate-controlled in accordance with physiologicalvariables that are indirectly reflective of the body's metabolic ratesuch as body temperature, ventilation rate, or minute ventilation.Minute ventilation varies almost linearly with aerobic oxygenconsumption during exercise up to the anaerobic threshold and is thephysiological variable that is most commonly used in rate-adaptivepacemakers to reflect the exertion level of the patient.

[0023] An even more indirect indication of metabolic rate is provided bythe measurement of body activity or motion. Body activity is correlatedwith metabolic demand because such activity requires energy expenditureand hence oxygen consumption. An activity-sensing pacemaker uses apiezoelectric sensor or accelerometer inside the pacemaker case thatresponds to vibrations or accelerations by producing electrical signalsproportional to the patient's level of physical activity.

[0024] In such rate-adaptive pacemakers that vary the pacing rate inaccordance with a measured exertion level, the control system isgenerally implemented as an open-loop controller that maps a particularexertion level to one particular target heart rate, termed thesensor-indicated rate. The mapping is accomplished by a rate-responsecurve which is typically a linear function (i.e., a straight line), butcould also be some non-linear function as well such as a dual-slopecurve or exponential curve. The rate-response curve is then defined withminimum and maximum target heart rates. A minimum target heart rate fora patient can be ascertained clinically as a heart rate adequate tosustain the patient at rest, while a maximum allowable target heart rateis defined with a formula that depends on the patient's age. Therate-response curve then maps a resting exertion level to the minimumheart rate and maps the maximum exertion level attainable by thepatient, termed the maximum exercise capacity, to the maximum allowableheart rate. The responsiveness of the control system, defined as how thetarget heart rate changes with a given change in exertion level, dependsupon the slope of the rate-response curve (or slopes in the case of adual-slope curve) which is dictated by the defined maximum exercisecapacity. An under-responsive pacemaker will unnecessarily limitexercise duration and intensity in the patient because the heart ratewill not increase enough to match metabolic demand, while anover-responsive pacemaker can lead to palpitations and patientdiscomfort.

[0025] The responsiveness of a rate-adaptive pacemaker is controlled inaccordance with a rate-response curve RRC such as shown in FIG. 2A.Other embodiments may use a dual-slope curve or a non-linear curve asdescribed below. A change in exertion level as determined from a minuteventilation measurement causes a proportional change in the target heartrate in accordance with the slope of the curve, termed the responsefactor RF. The target heart rate is then used as a lower rate limit bythe pacemaker to pace the heart in accordance with a programmed pacingmode. As shown in the figure, the rate response curve maps a restingexertion level REL to a minimum target rate MinHR which corresponds tothe minimum LRL that is to be used by the pacemaker. The maximum targetrate MaxHR is the maximum rate at which the pacemaker is allowed to pacethe heart and is mapped to by the rate response curve from the maximumexertion level the patient is expected to be able to reach, referred toas the maximum exercise capacity MEC. In the single-slope rate responsecurve shown in FIG. 2, the response factor RF may then be defined as:

RF=(MaxHR−MinHR)/(MEC−REL)

[0026] The responsiveness of the pacemaker can also be controlled inaccordance with a dual-slope rate response curve such as shown in FIG.2B. A change in exertion level EXL (as determined from either minuteventilation or body activity) causes a change in the sensor indicatedrate that is proportional to the slope of the response curve. The slopeof the rate response curve is designated the initial response factor RFbelow the heart rate breakpoint HRB, and designated the high rateresponse factor HRRF above HRB. The heart rate breakpoint HRB ideallyshould be set to correspond to an exertion level equal to the anaerobicthreshold AT of the patient. The anaerobic threshold is the level ofexertion above which the concentration of lactic acid produced byanaerobic metabolism starts to build up rapidly in the blood. It thusrepresents an exertion level at which the body starts to utilize oxygenless efficiently and, along with maximal oxygen consumption, is a usefulindex of current physical conditioning. The responsiveness of thepacemaker below the anaerobic threshold as defined by RF should begreater than that above the threshold as defined by HRRF so thatoverpacing above the anaerobic threshold can be avoided.

[0027] 3. Resynchronization Therapy

[0028] Cardiac resynchronization therapy is pacing stimulation appliedto one or more heart chambers in a manner that restores or maintainssynchronized contractions of the atria and/or ventricles and therebyimproves pumping efficiency. Certain patients with conductionabnormalities may experience improved cardiac synchronization withconventional single-chamber or dual-chamber pacing as described above.For example, a patient with left bundle branch block may have a morecoordinated contraction of the ventricles with a pace than as a resultof an intrinsic contraction. Resynchronization pacing, however, may alsoinvolve delivering paces to multiple sites of a heart chamber or pacingboth ventricles and/or both atria in accordance with a resynchronizationpacing mode as described below. Ventricular resynchronization pacing isuseful in treating heart failure because, although not directlyionotropic, resynchronization results in a more coordinated contractionof the ventricles with improved pumping efficiency and increased cardiacoutput. Resynchronization pacing of the atria may also be beneficial incertain heart failure patients, particularly for preventing the onset ofatrial arrhythmias.

[0029] One way to deliver resynchronization therapy is to pace a sitewith a synchronous bradycardia pacing mode and then deliver one or moreresynchronization paces to one or more additional pacing sites in adefined time relation to one or more selected sensing and pacing eventsthat either reset escape intervals or trigger paces in the bradycardiapacing mode. One such resynchronization pacing mode may be termed offsetresynchronization pacing. In this mode, a first site is paced with abradycardia mode, and a second site receives a resynchronization pace atan offset interval with respect to the pace delivered to the first site.The offset interval may be zero in order to pace both sitessimultaneously, positive in order to pace the first site after thesecond, or negative to pace the first site before the second. Forexample, in biventricular resynchronization pacing, one ventricle ispaced with a bradycardia mode while the contralateral ventricle receivesresynchronization paces at the specified biventricular offset interval.The offset interval would normally be individually specified to optimizecardiac output in a particular patient. Ventricular resynchronizationcan also be achieved in certain patients by pacing at a singleunconventional site, such as the left ventricle instead of the rightventricle. In such a mode, right ventricular senses may be used totrigger left ventricular paces or used to define an escape interval thatupon expiration causes delivery of a left ventricular pace.

[0030] In a particular implementation of cardiac resynchronizationtherapy, one atrium and/or one ventricle are designated as ratechambers, and paces are delivered to the rate chambers based upon pacingand sensed intrinsic activity in the chamber in accordance with thebradycardia pacing mode. In a single-chamber bradycardia pacing mode,for example, one of the paired atria or one of the ventricles isdesignated as the rate chamber. In a dual-chamber bradycardia pacingmode, either the right or left atrium is selected as the atrial ratechamber and either the right or left ventricle is selected as theventricular rate chamber. The heart rate and the escape intervals forthe pacing mode are defined by intervals between sensed and paced eventsin the rate chambers only. Resynchronization therapy may then beimplemented by adding synchronized pacing to the bradycardia pacing modewhere paces are delivered to one or more synchronized pacing sites in adefined time relation to one or more selected sensing and pacing eventsthat either reset escape intervals or trigger paces in the bradycardiapacing mode. In bilateral synchronized pacing, which may be eitherbiatrial or biventricular synchronized pacing, the heart chambercontralateral to the rate chamber is designated as a synchronizedchamber. For example, the right ventricle may be designated as the rateventricle and the left ventricle designated as the synchronizedventricle, and the paired atria may be similarly designated. Eachsynchronized chamber is then paced in a timed relation to a pace orsense occurring in the contralateral rate chamber.

[0031] 4. Hardware Platform

[0032] Pacemakers are typically implanted subcutaneously orsubmuscularly in a patient's chest and have leads threaded intravenouslyinto the heart to connect the device to electrodes used for sensing andpacing. (As used herein, the term pacemaker should be taken to mean anycardiac rhythm management device with a pacing functionality includingan implantable cardioverter/defibrillator that includes a pacemaker.)Leads may also be positioned on the epicardium by various means. Aprogrammable electronic controller causes the pacing pulses to be outputin response to lapsed time intervals and sensed electrical activity(i.e., intrinsic heart beats not as a result of a pacing pulse).Pacemakers sense intrinsic cardiac electrical activity by means ofinternal electrodes disposed near the chamber to be sensed. Adepolarization wave associated with an intrinsic contraction of theatria or ventricles that is detected by the pacemaker is referred to asan atrial sense or ventricular sense, respectively. In order to causesuch a contraction in the absence of an intrinsic beat, a pacing pulse(either an atrial pace or a ventricular pace) with energy above acertain pacing threshold is delivered to the chamber.

[0033] A particular implementation of a rate-adaptive pacemaker that mayalso be configured to deliver ventricular resynchronization therapy isshown in FIG. 1. A microprocessor 10 serves as the device controller andcommunicates with a memory 12 via a bidirectional data bus 13. Thememory 12 typically comprises a ROM or RAM for program storage and a RAMfor data storage. The controller senses cardiac events through a sensingchannel and outputs pacing pulses to the heart via a pacing channel inaccordance with a programmed pacing mode. Sensing and/or pacing channelsinclude the leads made up of electrodes on a catheter or wire thatconnect the pacemaker to the heart. In this embodiment, the pacemakerhas atrial sensing and pacing channels comprising electrode 34, lead 33,sensing amplifier 31, pulse generator 32, and an atrial channelinterface 30 which communicates bidirectionally with a port ofmicroprocessor 10. The device also has sensing and pacing channels foreach ventricle comprising electrodes 24 a-b, leads, sensing amplifiers21 a-b, pulse generators 22 a-b, and ventricular channel interfaces 20a-b, where “a” and “b” refer to components associated with the left orright ventricle, respectively. For each channel, the same lead andelectrode are used for both sensing and pacing. The channel interfaces20 and 30 may include analog-to-digital converters for digitizingsensing signal inputs from the sensing amplifiers and registers whichcan be written to by the microprocessor in order to output pacingpulses, change the pacing pulse amplitude, and adjust the gain andthreshold values for the sensing amplifiers. A telemetry interface 40 isalso provided for communicating with an external programmer.

[0034] The controller 10 controls the overall operation of the device inaccordance with programmed instructions stored in memory, includingcontrolling the delivery of paces via the pacing channels, interpretingsense signals received from the sensing channels, and implementingtimers for defining escape intervals and sensory refractory periods. Thesensing circuitry of the pacemaker detects a chamber sense, either anatrial sense or ventricular sense, when a sense signal (i.e., a voltagesensed by an electrode representing cardiac electrical activity,sometimes called an electrogram signal) generated by a particularchannel exceeds a specified intrinsic detection threshold. Pacingalgorithms used in particular pacing modes employ such senses to triggeror inhibit pacing. A minute ventilation sensor MVS and an accelerometerAC are employed to sense the minute ventilation and body activity,respectively. The pacemaker uses the sensed minute ventilation and/orthe accelerometer signal to adjust the rate at which the pacemaker pacesthe heart in the absence of a faster intrinsic rhythm. Themicroprocessor 10 executes programmed instructions that implementvarious pacing and rate-adaptive algorithms in accordance withparameters that define the pacing mode and pacing configuration, thelatter referring to which of the available channels are to be used forsensing and/or pacing. The microprocessor is also programmed toimplement the method for adjusting these parameters in accordance withmeasurements of the minute ventilation oscillations as described below.

[0035] 5. Optimization of Rate-adaptive Pacing

[0036] One embodiment of the present invention involves the automaticsetting of the rate-response curve breakpoint at the anaerobic thresholdas determined by the point at which an oscillatory minute ventilationpattern disappears when a patient exercises with increasing intensity.FIG. 4 illustrates an exemplary implementation of the method. At stepA1, the minute ventilation signal MV is input to a bandpass filter thatextracts the frequency components of the signal that are betweenapproximately 0.01 and 0.05 Hz. This corresponds to the frequency ofoscillations in minute ventilation that have been found to occur inheart failure patients. At step A2, the mean amplitude of the extractedfrequency components are calculated, and this value is compared to aspecified threshold value at step A3. If the amplitude of theoscillations is below the threshold, the slope of the rate-responsecurve is programmed at step A4 to a value corresponding to what isappropriate when the patient is exercising above the anaerobicthreshold. If the amplitude of the oscillations is above the threshold,the slope of the rate-response curve is set to a value appropriate forexercise below the anaerobic threshold at step A5. The sensor-indicatedrate is calculated by processing the MV signal at step A8, setting theslope of the rate-response curve at step A6 in accordance with theresults of either step A5 or step A4, and mapping of the minuteventilation to a sensor-indicated rate at step A7.

[0037] In another embodiment of the invention, an activity levelmeasurement taken with a motion or pressure sensor such as anaccelerometer is associated with a simultaneously taken minuteventilation measurement. The minute ventilation measurement is thencross-checked with the associated activity level measurement toascertain if the minute ventilation measurement if reflective of thepatient's true exertion level or is a result of the patient'soscillatory minute ventilation pattern. A mapping based upon eitherpopulation data or an assessment of the individual patient may be usedthat relates a particular activity level to a particular percentage ofthe patient's minute ventilation reserve. The minute ventilation reserveis defined as the difference between the patient's maximum minuteventilation level and the minute ventilation level corresponding torest. For example, a linear mapping may be used with a no-activitymeasurement value mapped to 0 percent of the reserve (i.e., the restingexertion level), a maximum activity measurement value mapped to 100percent of the reserve (i.e., the maximum exercise capacity), andlinearly interpolated values therebetween. Such a mapping thus allows adirect comparison between a minute ventilation measurement and acorresponding activity level measurement. Alternatively, ranges ofminute ventilation values may be associated with particular ranges ofactivity levels to allow cross-checking of minute ventilationmeasurements.

[0038] 6. Evaluation and Adjustment of Resynchonization Therapy

[0039] As aforesaid, it has been found that effective resynchronizationtherapy reduces the magnitude of the oscillatory minute ventilationpattern in heart failure patients. Accordingly, another embodiment ofthe invention involves the monitoring of minute ventilation oscillationsso that the effectiveness of resynchronization pacing can be evaluated.Such information can be used by a clinician to then adjust variousresynchronization pacing parameters. Alternatively, such parameters canbe adjusted automatically by the device controller based upon whichresynchronization pacing modes result in the greatest decrease inoscillatory minute ventilation. Such parameters may include, forexample, the pacing configuration (i.e., which of the available pacingchannels are used for pacing), the AV interval in atrial tracking and/oratrio-ventricular sequential pacing modes, the biventricular offsetinterval in biventricular pacing modes, as well as rate-adaptive pacingparameters as described above.

[0040] Although the invention has been described in conjunction with theforegoing specific embodiment, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Such alternatives, variations, and modifications are intended to fallwithin the scope of the following appended claims.

What is claimed is:
 1. A method for adjusting the responsiveness of arate-adaptive pacemaker operating in a patient, wherein measured minuteventilation values in the patient are mapped to a pacing rate by adual-slope rate response curve, comprising: measuring minute ventilationvalues and determining that an average of those minute ventilationvalues are increasing, signifying that the patient's exertion level isincreasing; determining an amplitude of an oscillatory component in themeasured minute ventilation values to be above a specified thresholdvalue; and, if the amplitude of the oscillatory component falls belowthe specified threshold value as the average minute ventilationcontinues to increase, setting the breakpoint of the rate response curveequal to the presently measured minute ventilation value.
 2. The methodof claim 1 wherein the measured minute ventilation values are passedthrough a high pass filter to determine the oscillatory component. 3.The method of claim 2 wherein the oscillatory component is in anapproximate frequency range between 0.01 and 0.05 Hz.
 4. A method foroperating a pacemaker in a patient, comprising: sensing ventriculardepolarizations and resetting a ventricular escape interval upon eachventricular sense; delivering paces to a ventricle such that aventricular pace is delivered upon expiration of the ventricular escapeinterval, the reciprocal of the ventricular escape interval being thelower rate limit of the pacemaker; measuring minute ventilation valuescorresponding to the exertion level of the patient; determining if anamplitude of an oscillatory component in the measured minute ventilationvalues is above a specified threshold value; if the amplitude of theoscillatory component is below the specified threshold value, adjustingthe lower rate limit in accordance with the measured minute ventilationvalue; and, if the amplitude of the oscillatory component is above thespecified threshold, cross-checking the measured minute ventilationvalue with a measured activity level before adjusting the lower ratelimit.
 5. A method for operating a pacemaker in a patient, comprising:sensing depolarizations from both ventricles; pacing both ventricles inaccordance with a ventricular resynchronization pacing mode; measuringminute ventilation values corresponding to the exertion level of thepatient; and, determining if an amplitude of an oscillatory component inthe measured minute ventilation values is above a specified thresholdvalue.
 6. The method of claim 5 further comprising transmitting anindication of the amplitude of the oscillatory component to an externalprogrammer.
 7. The method of claim 5 further comprising adjusting anoperating parameter of the pacemaker if the amplitude of the oscillatorycomponent in the measured minute ventilation values is above a specifiedthreshold value.
 8. The method of claim 7 wherein the adjusted operatingparameter is an atrio-ventricular interval.
 9. The method of claim 7wherein the adjusted operating parameter is a biventricular offsetinterval.
 10. A rate-adaptive pacemaker, comprising; sensing and pacingchannels for sensing cardiac depolarizations and delivering paces to aselected chamber; a minute ventilation sensor, a controller forcontrolling the delivery of paces in accordance with a pacing mode at aprogrammed pacing rate, wherein measured minute ventilation values inthe patient are mapped to a pacing rate by a dual-slope rate responsecurve; wherein the controller is configured to determine if an amplitudeof an oscillatory component in the measured minute ventilation values isabove a specified threshold value and, if the amplitude of theoscillatory component falls below the specified threshold value as theaverage minute ventilation continues to increase, to set the breakpointof the rate response curve equal to the presently measured minuteventilation value.
 11. The pacemaker of claim 10 further comprising abandpass filter for extracting the oscillatory component from themeasured minute ventilation values.
 12. The pacemaker of claim 10wherein the filter has a passband in an approximate frequency rangebetween 0.01 and 0.05 Hz.
 13. A rate-adaptive pacemaker, comprising:sensing and pacing channels for sensing cardiac depolarizations anddelivering paces to a selected chamber; a minute ventilation sensor, acontroller for controlling the delivery of paces in accordance with apacing mode at a programmed pacing rate, wherein measured minuteventilation values in the patient are mapped to a pacing rate by a rateresponse curve; wherein the controller is programmed to determine if anamplitude of an oscillatory component in the measured minute ventilationvalues is above a specified threshold value and, if the amplitude of theoscillatory component is below the specified threshold value, to adjustthe lower rate limit in accordance with the measured minute ventilationvalue and, if the amplitude of the oscillatory component is above thespecified threshold, to cross-check the measured minute ventilationvalue with a measured activity level before adjusting the lower ratelimit.
 14. A pacemaker, comprising: sensing channels for sensingdepolarizations from both ventricles; pacing channels for deliveringpaces to both ventricles; a minute ventilation sensor; a controller forpacing the ventricles in accordance with a ventricular resynchronizationpacing mode; and, wherein the controller is configured to measure minuteventilation values corresponding to the exertion level of the patientand to determine if an amplitude of an oscillatory component in themeasured minute ventilation values is above a specified threshold value.15. The pacemaker of claim 14 further comprising a telemetry interfacefor transmitting an indication of the amplitude of the oscillatorycomponent to an external programmer.
 16. The pacemaker of claim 14wherein the controller is configured to adjust an operating parameter ofthe pacemaker if the amplitude of the oscillatory component in themeasured minute ventilation values is above a specified threshold value.17. The pacemaker of claim 16 wherein the operating parameter adjustedby the controller is an atrio-ventricular interval.
 18. The pacemaker ofclaim 16 wherein the operating parameter adjusted by the controller is abiventricular offset interval.
 19. The pacemaker of claim 16 wherein theoperating parameter adjusted by the controller is a pacing configurationthat determines which pacing channels are to be used for pacing.
 20. Thepacemaker of claim 16 wherein the operating parameter adjusted by thecontroller is a rate-adaptive pacing parameter.